Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment

Barg, Assaf Arie; Livnat, Tami; Kenet, Gili

doi:10.1182/blood.2023020721

Cited by 6 publications

(1 citation statement)

References 86 publications

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“…The clinical history is the best predictor of the bleeding tendency and helps avoid unnecessary treatments [ 76 ]. Cases with FXI activity below 20 IU/dL sometimes develop surgical bleeding, particularly in sites rich in fibrinolytic activity [ 17 ].…”

Section: Fxi Deficiencymentioning

confidence: 99%

Rare inherited coagulation disorders: no longer orphan and neglected

Mohsenian,

Mannucci,

Menegatti

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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Section: Fxi Deficiencymentioning

confidence: 99%

Rare inherited coagulation disorders: no longer orphan and neglected

Mohsenian,

Mannucci,

Menegatti

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre

Wu,

Cacciola‐Price,

Goldberg

et al. 2024

Haemophilia

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IntroductionThe management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications.AimsTo evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri‐procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported.MethodsRetrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed.ResultsWe identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1–8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis.ConclusionsCurrent management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.

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Targeting factor XI and factor XIa to prevent thrombosis

Gailani,

Gruber

2024

Blood

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Direct oral anticoagulants (DOACs) that inhibit the coagulation proteases thrombin or factor Xa have replaced warfarin and other vitamin K antagonists (VKA) for most indications requiring long-term anticoagulation. In many clinical situations, DOACs are as effective as VKAs, cause less bleeding, and do not require laboratory monitoring. However, because DOACs target proteases that are required for hemostasis, their use increases the risk of serious bleeding. Concerns over therapy-related bleeding undoubtedly contribute to under-treatment of many patients who would benefit from anticoagulation therapy. There is considerable interest in the plasma zymogen factor XI (FXI) and its protease form factor XIa (FXIa) as drug targets for treating and preventing thrombosis. Laboratory and epidemiologic studies support the conclusion that FXI contributes to venous and arterial thrombosis. Based on seventy years of clinical observations of patients lacking FXI, it is anticipated that drugs targeting this protein will cause less severe bleeding than warfarin or DOACs. In phase 2 studies, drugs that inhibit FXI or FXIa prevent venous thromboembolism after total knee arthroplasty as well as, or better than, low molecular weight heparin. Patients with heart disease on FXI/XIa inhibitors experienced less bleeding than patients on DOACs. Based on these early results, phase 3 trials have been initiated that compare drugs targeting FXI and FXIa to standard treatments or placebo. Here we review the contributions of FXI to normal and abnormal coagulation and discuss results from pre-clinical, nonclinical, and clinical studies of FXI and FXIa inhibitors.

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Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment

Cited by 6 publications

References 86 publications

Rare inherited coagulation disorders: no longer orphan and neglected

Rare inherited coagulation disorders: no longer orphan and neglected

Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre

Targeting factor XI and factor XIa to prevent thrombosis

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